Noninvasive imaging of lupus nephritis disease activity

Dr. Gale will use this LRA Lupus Innovation Award to address the significant unmet need for a noninvasive imaging technology to diagnose and monitor kidney disease caused by lupus known as lupus nephritis.

Currently, removing a small piece of kidney tissue by a surgical biopsy is the only method to diagnose and monitor lupus nephritis. This invasive procedure comes with some risks, and the pieces of tissue removed during the biopsy do not necessarily show the health status of the whole kidney. Since many lupus nephritis patients progress to end-stage renal disease, monitoring the kidneys with a noninvasive method would help doctors improve patient outcomes.

Dr. Gale’s team will test their recently invented unique contrast dye that can clearly visualize lupus nephritis through a magnetic resonance imaging (MRI) procedure.

What this study means for people with lupus

This study is designed to provide a safer and more effective way for doctors to diagnose and monitor lupus patients for lupus nephritis disease activity.

Lupus nephritis, kidney inflammation caused by systemic lupus erythematosus (SLE), occurs in roughly ½ of patients suffering SLE and represents a major risk factor for lupus morbidity and mortality. Lupus nephritis (LN) is an insidious manifestation of SLE that is difficult to manage based on clinical signs alone. Definitive diagnosis of lupus nephritis disease activity requires core needle biopsy, which is invasive, poses substantial procedural risk, and samples only a small, sometimes non-representative, portion of the kidney. Invasive biopsy is a powerful tool to establish lupus nephritis diagnosis but is not practical to monitor chronic disease. The lack of non-invasive diagnostic tools for lupus nephritis poses a real challenge, with potentially disastrous consequences. For example, nearly ½ of in patients with Class IV LN, the most prevalent form of lupus nephritis, will progress to end stage renal disease within 15 years. On the other hand, for cases where histologically confirmed remission is achieved, 10-year survival rates improve from 46% to 95%. Unfortunately, lupus nephritis disease activity may persist in patients who do not display symptoms or who appear to respond to therapy based on clinical signs. Physicians managing lupus nephritis patients are forced to make decisions based on clinical signs alone or subject patients to repeat invasive biopsy.
There is a major, unmet need for non-invasive imaging technology to diagnose lupus nephritis disease activity. Pathologic changes associated with lupus nephritis are not abundantly visible using conventional magnetic resonance imaging (MRI), ultrasound, or X-computed tomography. Molecular imaging of disease activity is very technically challenging, as most molecularly targeted tracer molecules are excreted through the kidneys, generating high non-specific background signal that confounds image analysis. We recently invented new MR imaging probe technology that will provide an instantaneous, background-free imaging readout of lupus nephritis disease activity.
The objective of the proposed research is to develop an imaging biomarker to non-invasively diagnose, map and longitudinally monitor lupus nephritis disease activity.
Aim 1. Establish proof of concept imaging in murine model of lupus nephritis.
Aim 2. Screen imaging probe candidates and optimize the imaging dose.
Aim 3. Image lupus nephritis disease progression and treatment response.